STRUCTURAL CHARACTERIZATION OF A 4-HYDROXY-2-ALKENAL-DERIVED FLUOROPHORE THAT CONTRIBUTES TO LIPOPEROXIDATION-DEPENDENT PROTEIN CROSS-LINKING IN AGING AND DEGENERATIVE DISEASE

Modification of proteins by products of lipid peroxidation results in various fluorescent adducts associated with oxidative stress pathophys iology in degenerative disease. Using n-butylamine as a model for the lysine side chain, the structure of the probable major ex/em 360/430-n m fluorophore that arises from cross-linking of two protein-based lysi nes by one 4-hydroxy-2-alkenal is shown to be a 2-alkyl-2-hydroxy-1,2- dihydropyrrol-3-one iminium. That this fluorophore can be independentl y generated in higher yield from either 4-oxo-2-alkenals or 3,4-dioxoa lkanals supports a proposed mechanistic pathway that involves two 2e o xidations following initial Schiff base formation.